The proposed project consists of a study of the physiology of synapses developing in vivo. The objective is to gain an understanding of the process involved in the formation, maturation and long-term maintenance of synaptic contacts. Particular attention will be paid to the specific changes in physiology and morphology which occur during development. We will examine such features as electrical coupling between developing muscle fibers, the timecourse of innervation, the occurrence of errors in innervation and the correction of such errors. We shall consider whether there is a time during development when neurones retract processes and are unable to regenerate new ones. These studies will be conducted primarily on normally developing rat embryos. We shall also maintain in vitro explants of embryonic tissue which include spinal cord with ribcage attached. We shall ask whether in such a controlled environment the innervation of intercostal muscles proceeds as normal. We will also make specific manipulations to perturb this development. In addition we will continue to examine the development of nerve-nerve synapses by studying reinnervation of autonomic ganglion cells in adult frogs.